ArticleThe Journal of clinical investigation2014
Lysosomal β-glucuronidase regulates Lyme and rheumatoid arthritis severity.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Spirulina supplementation and rheumatoid arthritis: A systematic review of current research and molecular mechanisms.Molecular biology reports · 2025Pooled it
- Mostly getting along -Borrelia burgdorferi and its manipulation of the host immune system.ImmunoHorizons · 2026Review
- Curiouser and curiouser: understanding the intersection of inter- and intra-specific diversity during theInfection and immunity · 2026Review
- Non-invasive profiling of exosomal miRNA and protein biomarkers from vaginal discharge for the early detection of preterm labor.Journal of nanobiotechnology · 2026Article
- Strain-specific immune response patterns toInfection and immunity · 2026Article
- Comparative Effects of Turmeric Secondary Metabolites Across Resorptive Bone Diseases.Metabolites · 2025Article
- A comparison of genome-wide association analyses of persistent symptoms after Lyme disease, fibromyalgia, and myalgic encephalomyelitis - chronic fatigue syndrome.BMC infectious diseases · 2025Article
- Toll-like receptor 1 polymorphism is associated with impaired immune tolerance, dysregulated inflammatory responses toFrontiers in immunology · 2025Article
- Single-cell RNA sequencing of murine ankle joints over time reveals distinct transcriptional changes followingiScience · 2023Article
- Endogenous Linear Plasmids lp28-4 and lp25 Are Required for Infectivity and Restriction Protection in the Lyme Disease Spirochete Borrelia mayonii.Infection and immunity · 2023Article
- Article
- CD4 T cell responses in persistent Borrelia burgdorferi infection.Current opinion in immunology · 2022Review
- The Cdkn2a gene product p19 alternative reading frame (p19ARF) is a critical regulator of IFNβ-mediated Lyme arthritis.PLoS pathogens · 2022Article
- Pathogenesis of Borrelia burgdorferi and Babesia microti in TLR4-Competent and TLR4-dysfunctional C3H mice.Cellular microbiology · 2021Article
- Lyme arthritis: linking infection, inflammation and autoimmunity.Nature reviews. Rheumatology · 2021Review
- Genetic Background Amplifies the Effect of Immunodeficiency in Antibiotic Efficacy Against Borrelia burgdorferi.The Journal of infectious diseases · 2021Article
- The beta-glucuronidase intracisternal A particle insertion model results in similar overall MPSVII phenotype as the single base deletion model when on the same C57BL/6J mouse background.Molecular genetics and metabolism reports · 2021Article
- Immune Response toCurrent issues in molecular biology · 2021Article
- NK cell-derived GM-CSF potentiates inflammatory arthritis and is negatively regulated by CIS.The Journal of experimental medicine · 2020Article
- Therapeutic significance of β-glucuronidase activity and its inhibitors: A review.European journal of medicinal chemistry · 2020Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Lyme disease, caused by the spirochete Borrelia burgdorferi, is the most prevalent arthropod-borne illness in the United States and remains a clinical and social challenge. The spectrum of disease severity among infected patients suggests that host genetics contribute to pathogenic outcomes, particularly in patients who develop arthritis. Using a forward genetics approach, we identified the lysosomal enzyme β-glucuronidase (GUSB), a member of a large family of coregulated lysosomal enzymes, as a key regulator of Lyme-associated arthritis severity. Severely arthritic C3H mice possessed a naturally occurring hypomorphic allele, Gusbh. C57BL/6 mice congenic for the C3H Gusb allele were prone to increased Lyme-associated arthritis severity. Radiation chimera experiments revealed that resident joint cells drive arthritis susceptibility. C3H mice expressing WT Gusb as a transgene were protected from severe Lyme arthritis. Importantly, the Gusbh allele also exacerbated disease in a serum transfer model of rheumatoid arthritis. A known GUSB function is the prevention of lysosomal accumulation of glycosaminoglycans (GAGs). Development of Lyme and rheumatoid arthritis in Gusbh-expressing mice was associated with heightened accumulation of GAGs in joint tissue. We propose that GUSB modulates arthritis pathogenesis by preventing accumulation of proinflammatory GAGs within inflamed joint tissue, a trait that may be shared by other lysosomal exoglycosidases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.